Lack of involvement of P-glycoprotein (P-gp) in pemphigus patients with poor response to steroid therapy
Lack of involvement of P-glycoprotein (P-gp) in pemphigus patients with poor response to steroid therapy
复制标题
DOI：
10.1016/s0923-1811(01)00169-4
复制
发表时间：
2002-04-01
影响因子：
4.6
通讯作者：
González-Amaro, R
中科院分区：
文献类型：
--
作者：
de la Fuente, H;Baranda, L;González-Amaro, R
一小部分天疱疮患者对类固醇治疗没有充分的反应。P-糖蛋白（或P-gp）是一种细胞膜外排泵，可将药物（包括糖皮质激素）从细胞溶质排出至细胞外介质。淋巴细胞中P-糖蛋白的表达和/或功能增加可降低糖皮质激素的细胞内浓度，从而降低其治疗效果。本研究的目的是评估P-糖蛋白在激素治疗反应良好和不良的天疱疮患者的单个核细胞（MNC）中的表达和活性。我们研究了20例寻常型天疱疮患者，其中8例被归类为激素治疗的不良反应者，12例被归类为激素治疗的良好反应者。用流式细胞术定量分析MNC中P-糖蛋白的表达和活性，用半定量RT-PCR技术测定P-糖蛋白mRNA水平。我们发现P-糖蛋白在mRNA和蛋白水平的表达在激素治疗反应良好和不良的天疱疮患者中是相似的。关于P-糖蛋白活性获得了类似的结果。在某些天疱疮患者中，P-糖蛋白似乎与类固醇治疗的不良反应无关。重要的是要调查其他机制，可以解释糖皮质激素抵抗在一些天疱疮患者。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
A small but significant fraction of pemphigus patients do not show an adequate response to steroid therapy. P-glycoprotein (or P-gp) is a cell membrane efflux pump that expels drugs, including glucocorticoids, from the cytosol to the extracellular medium. An increased expression and/or function of P-glycoprotein in lymphoid cells could decrease the intracellular concentration of glucocorticoids, diminishing its therapeutic effects. The aim of this work was to assess the expression and activity of P-glycoprotein in the mononuclear cells (MNC) from pemphigus patients with good and poor response to steroid therapy. We studied 20 patients with pemphigus vulgaris, eight of them classified as poor responders and 12 as good responders to steroid therapy. The expression and activity of P-glycoprotein by MNC were quantified by flow cytometry, and P-glycoprotein mRNA levels were determined by a semi- quantitative RT-PCR technique. We found that the expression of P-glycoprotein at both mRNA and protein levels was similar in pemphigus patients with good and poor response to steroid therapy. Similar results were obtained regarding P-glycoprotein activity. P-glycoprotein does not seem to be involved in the poor response to steroid treatment seen in some pemphigus patients. It is important to investigate additional mechanisms that could account for the glucocorticoid resistance seen in some pemphigus patients. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.